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Biomedical subjects

T Goromaru

Publications and source records attributed to T Goromaru.

At least 37 records · Page 2Linked to original sources
PubMed1990

Preparation of [3H]6-nitroquipazine, a potent and selective 5-hydroxytryptamine uptake inhibitor.

The synthesis of 6-nitroquipazine, a very potent and selective 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor, labeled with tritium is described. High specific activity [3H]6-nitroquipazine could be prepared by the nitration of [3H]quipazine using a mixture of equal volumes of sulfuric acid and nitric acid. The radiochemical yield was approximately 50% based on [3H]quipazine. The radiochemical purity was more than 95% from high performance liquid chromatography(HPLC) and thin layer chromatography(TLC) determinations. [3H]6-Nitroquipazine would be a new suitable radioligand for studying 5-HT transporter complex in brain and platelets.

Quinolines↗
PubMed1990

Evaluation of 3H-paroxetine as a radioligand for in vivo study of 5-hydroxytryptamine uptake sites in mouse brain.

The distribution of radioactivity in the mouse brain after intravenous administration of 3H-paroxetine was in the order (highest to lowest) hypothalamus greater than cerebral cortex greater than cerebellum. The radioactivity in the hypothalamus and cerebral cortex after injection of 3H-paroxetine was significantly decreased by treatment with 6-nitroquipazine or paroxetine. HPLC and TLC analyses show that no radioactive metabolites were found in the mouse brain 3 h after intravenous administration of 3H-paroxetine. The present results indicate that 3H-paroxetine would be a suitable radioligand for in vivo study of 5-HT uptake sites in mouse brain.

Animals↗
PubMed1990

In vivo labeling of 5-hydroxytryptamine uptake sites in mouse brain with [3H]-6-nitroquipazine.

6-Nitroquipazine (DU 24565; 6-nitro 2-piperazinylquinoline) is a very potent 5-hydroxytryptamine (5-HT; serotonin) uptake inhibitor. It has been demonstrated very recently that [3H]-6-nitroquipazine is a suitable radioligand for studying 5-HT uptake sites. The present study evaluates [3H]6-nitroquipazine as a radioligand for in vivo labeling of 5-HT uptake sites in mouse brain. Very high uptake of radioactivity in the brain after i.v. administration of [3H]-6-nitroquipazine was shown. Regional distribution of the radioactivity in mouse brain 3 hr after injection of [3H]-6-nitroquipazine was in the order (highest to lowest) hypothalamus greater than midbrain greater than striatum greater than hippocampus greater than cerebral cortex greater than medulla oblongata greater than cerebellum. The regional distribution of in vivo [3H]-6-nitroquipazine binding in mouse brain was highly correlated with that in rat brain obtained from previous in vitro binding studies. Coadministration of carrier 6-nitroquipazine (5 mg/kg) significantly decreased the radioactivity in the hypothalamus, whereas that in the cerebellum and cerebral cortex was increased. Because the cerebellum has very low density of [3H]-6-nitroquipazine binding sites, the radioactivity in the cerebellum could, therefore, reflect the amount on nonspecific binding and free ligand. Kinetic studies showed highest in vivo specific binding 1 hr after injection of [3H]-6-nitroquipazine and slow clearance of specific binding. Specific binding in the hypothalamus was inhibited in a stereoselective manner by the stereoisomers of norzimelidine. Furthermore, specific binding in the hypothalamus was reduced by several 5-HT uptake inhibitors, in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

[Evaluation of 3H-paroxetine as a radiopharmaceutical for lung function].

The potential of 3H-paroxetine as a radiotracer for in vivo study of the function in mouse lung was examined. A high accumulation of radioactivity in the mouse lung was observed after intravenous administration of 3H-paroxetine. However, the distributions of radioactivity in the mouse lung were not significantly decreased by treatment with paroxetine or other monoamine uptake inhibitors (6-nitroquipazine, desipramine and GBR 12909). It was found that the radioactivity in the mouse lung at 1 hr after intravenous administration of 3H-paroxetine was due to unmetabolized 3H-paroxetine from TLC and HPLC analyses. Furthermore, 3H-paroxetine exhibits both saturable and high affinity binding sites in mouse lung with a maximal number of binding sites (Bmax) of 303 fmoles/mg protein and a dissociation constant (Kd) of 92.2 pM. These results suggest that 3H-paroxetine would be a suitable radiopharmaceutical for in vivo study of the function of lung as a metabolic organ of serotonin.

Animals↗
PubMed1988

Changes in in vivo binding of 3H-Ro 15-1788 in mouse brain by reserpine.

The effects of reserpine on the in vivo binding of 3H-Ro 15-1788, (Ro 15-1788:ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate) a selective benzodiazepine antagonist, in the mouse brain were investigated. The biodistributions of tracer amounts of 3H-Ro 15-1788 in mice were significantly altered by pretreatment with reserpine (2.5 or 5.0 mg/kg, 24 h before the tracer administration). The time courses of radioactivity in the brain and the blood following i.v. injection of 3H-Ro 15-1788 with carrier Ro 15-1788 were not changed by pretreatment with reserpine, which suggested that the specific binding process might be altered by reserpine. The degree of alteration in the in vivo binding of 3H-Ro 15-1788 seemed to be dependent upon the dose of reserpine and the duration after the treatment of reserpine. The maximum changes in the biodistribution of 3H-Ro 15-1788 were observed at 1 day after injection of reserpine. The body temperature and the brain monoamine contents (dopamine, norepinephrine and 5-hydroxytryptamine) in mice were measured as indicators of pharmacological effects of reserpine, and good relationships to the degree of changes in the biodistribution of 3H-Ro 15-1788 and either the body temperature or brain monoamine contents, were observed. Furthermore, the changes in the biodistribution of 3H-Ro 15-1788 in the reserpinized mice were significantly suppressed by anti-depressant imipramine treatment. These results suggest that it would be possible to detect the in vivo drug interaction with brain benzodiazepine receptors in the living human brain using 11C-Ro 15-1788 and positron emission tomography (PET).

Animals↗
PubMed1984

Biohydroxylation of aminopyrine: quantitative studies of 3-hydroxymethyl metabolite in rats.

Significance of the formation of 4-dimethylamino-3-hydroxymethyl-2-methyl-1-phenyl-3-pyrazolin-5-on e (AM-3-CH2OH) for the metabolism of AM was examined quantitatively in rats. Although urinary excretion of AM-3-CH2OH accounted for only 0.7% to the dose, incubation of AM in the isolated hepatocyte system resulted in the formation of 9% of AM-3-CH2OH. Furthermore, metabolic disappearance of AM-3-CH2OH in the same system was fast, indicating the properties of an intermediate metabolite. These results suggested that the metabolic pathways via AM-3-CH2OH are very important in the metabolism of AM.

Aminopyrine↗
PubMed1984

Identification and quantitative determination of fentanyl metabolites in patients by gas chromatography--mass spectrometry.

Although fentanyl has been used widely as a short-acting narcotic analgesic, its metabolism in humans has not been clarified. In this study, three fentanyl metabolites were identified in the urine of eight surgical patients receiving 0.3-0.5 mg of fentanyl intravenously. The metabolites 4-N-(N-propionylanilino)piperidine, 4-N-(N-hydroxypropionylanilino)piperidine and 1-(2-phenethyl)-4-N-(N-hydroxypropionylanilino)piperidine, and unchanged fentanyl were identified by GC-mass spectrometry in urine collected 6 h after administration. Fentanyl and its main metabolite, 4-N-(N-propionylanilino)piperidine, were determined quantitatively in the urine of five additional patients receiving 0.5 mg fentanyl intravenously. Urinary excretion of fentanyl and 4-N-(N-propionylanilino)-piperidine during the first 12 h after injection accounted for 0.3-4.0% and 26 to 55% of the dose, respectively.

Adult↗
PubMed1983

Studies on drug metabolism by use of isotopes XXVII: urinary metabolites of rutin in rats and the role of intestinal microflora in the metabolism of rutin.

Analysis of urinary metabolites of orally administered rutin (I) labeled with deuterium [( 2',5',6'-2H]rutin, rutin-d) was carried out by GLC-MS. In rat urine, 3-hydroxyphenylacetic acid (III), 3-methoxy-4-hydroxyphenylacetic acid (IV), 3,4-dihydroxyphenylacetic acid (V), 3,4-dihydroxytoluene (VI), and 3-(m-hydroxyphenyl)propionic acid (VIII) were identified as rutin metabolites and were differentiated from the corresponding endogeneous compounds. Unchanged I and quercetin (II) were not present in the urine. Rutin-d was injected intraperitoneally in rats, administered orally to neomycin-treated rats, and incubated in vitro with the intestinal contents of rats. The experiments suggested the involvement of intestinal microflora in the metabolism of orally administered I.

Animals↗
PubMed1981

Characteristic biotransformation of aminopyrine in rat when administered with barbital.

After the administration of aminopyrine with or without barbital to rats, aminopyrine and its main metabolites were detected in plasma and the brain by means of gas chromatography-mass spectrometry. It was clarified that a marked increase of 4-monomethylaminoantipyrine was observed in the case of coadministration of aminopyrine and barbital, while the plasma level of aminopyrine decreased significantly compared with single administration.

Aminopyrine↗